Reengineering the shape of the viral capsid could advance biomedicine, DNA and RNA origami nanostructures can be used to create proteins that coat viruses into specific shapes.
Biologists have discovered a way to control the size and shape of neurons by combining protein complexes with DNA-based templates. The resulting nanostructures may have applications in developing vaccines and delivering drugs into the body.
Viral capsid proteins—the proteins that protect the virus’s genome—can be used to build organized protein assemblies. However, their shape and geometry depend on the virus. Reprogramming these building blocks, regardless of the original viral structure, is an attractive opportunity for drug delivery and vaccine development.
The scientists took up the challenge by creating a “programmed genome” that the capsid protein could assemble into. To avoid distorting the variable genome and creating unexpected species, they used a complex DNA origami material. These structures are only 1100 nanometers long, but are made entirely of DNA, which is folded into the desired matrix shape.
“Our method is based on the electrostatic interaction between the negative charge of the DNA nanostructures and the charged domain of the capsid protein, combined with the interaction between individual proteins. By changing the number of proteins used, we can greatly adjust the number of proteins in the structure, which wraps around DNA origami,” says Iris Seitz, lead author and PhD student at Aalto University.
“Using DNA origami as a template, we can direct the capsid protein into the size and shape defined by the user, creating well-defined assemblies, both in length and in diameter. By testing different forms of DNA origami, we also learned how the geometry of the form affects the whole assembly,” adds Seitz.
Professor Juha Huiskonen, an associate scientist at the University of Helsinki explains, “With the help of cryogenic electron microscopy, we can visualize the highly ordered substances during assembly and, in this case, measure even small changes in the assembly geometry resulting from different processes.” “We have discovered a simple and effective strategy to (re)direct the capsid protein to the desired shape.
Our method can be adapted and therefore not limited to one type of capsid protein, as we have shown that the capsid protein comes from four different viruses. Also, we can modify our model to be more relevant for the application, for example by combining RNA into origami, which will be translated into a useful or site-specific protein”, Professor Aalto Mauri Kostiainen, leader of the research project.
Although DNA origami structures are promising for the synthesis of biological processes, they suffer from instability, especially in the presence of DNA-degrading enzymes. In the experiments, however, “we can clearly see that the protein coat effectively protects the DNA nanostructures from DNA damage.
By combining the protection and functional characteristics of nucleic acid origami, including the ability to deliver DNA or messenger RNA and other cargo, we believe that our approach provides an interesting direction in the future for biomedical engineering,” Kostiainen concluded.
Source:Aalto Univeristy
